Prescribing Information

Adasuve (loxapine) Inhalation Powder is an antipsychotic used for the acute treatment of agitation associated with schizophrenia or bipolar I disorder in adults. Common side effects include changes in taste, sedation, and throat irritation.

Adasuve must be administered only under physician supervision. The recommended dose for acute agitation is 10 mg administered by oral inhalation, using a single-use inhaler. Adasuve may interact with other CNS depressants (e.g., alcohol, opioid analgesics, benzodiazepines, tricyclic antidepressants, general anesthetics, phenothiazines, sedative/hypnotics, muscle relaxants, and/or illicit CNS depressants), and other anticholinergic drugs. Tell your doctor all medications and supplements you use. During pregnancy, Adasuve should be used only if prescribed. It is unknown if this drug passes into breast milk. Consult your doctor before breastfeeding.

Our Adasuve (loxapine) Inhalation Powder Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What is Prescribing information?

The FDA package insert formatted in easy-to-find categories for health professionals and clinicians.

Clinical Trials Experience

Because clinical trials are conducted under widely
varying conditions, adverse reaction rates observed in the clinical trials of a
drug cannot be directly compared to rates in the clinical trials of another
drug and may not reflect the rates observed in clinical practice.

The following findings are based on pooled data from
three short-term (24-hour), randomized, double-blind, placebo-controlled
clinical trials (Studies 1, 2, and 3) of ADASUVE 10 mg in the treatment of
patients with acute agitation associated with schizophrenia or bipolar I disorder.
In the 3 trials, 259 patients received ADASUVE 10 mg, and 263 received placebo [see
Clinical Studies].

Commonly Observed Adverse Reactions

In the 3 trials in acute agitation, the most common
adverse reactions were dysgeusia, sedation, and throat irritation. These
reactions occurred at a rate of at least 2% of the ADASUVE group and at a rate
greater than in the placebo group. (Refer to Table 1).

Airway Adverse Reactions in the 3 Trials in Acute
Agitation

Agitated patients with Schizophrenia or Bipolar
Disorder: In the 3 short-term (24-hour), placebo-controlled trials in
patients with agitation associated with schizophrenia or bipolar disorder
(Studies 1, 2, and 3), bronchospasm (which includes reports of wheezing,
shortness of breath and cough) occurred more frequently in the ADASUVE group,
compared to the placebo group: 0% (0/263) in the placebo group and 0.8% (2/259)
in the ADASUVE 10 mg group. One patient with schizophrenia, without a history
of pulmonary disease, had significant bronchospasm requiring rescue treatment
with a bronchodilator and oxygen.

Bronchospasm and Airway Adverse Reactions in Pulmonary
Safety Trials

Clinical pulmonary safety trials demonstrated that
ADASUVE can cause bronchospasm as measured by FEV1, and as indicated by
respiratory signs and symptoms in the trials. In addition, the trials
demonstrated that patients with asthma or other pulmonary diseases, such as
COPD are at increased risk of bronchospasm. The effect of ADASUVE on pulmonary
function was evaluated in 3 randomized, double-blind, placebo-controlled
clinical pulmonary safety trials in healthy volunteers, patients with asthma,
and patients with COPD. Pulmonary function was assessed by serial FEV1 tests,
and respiratory signs and symptoms were assessed. In the asthma and COPD trials,
patients with respiratory symptoms or FEV1 decrease of ≥ 20% were
administered rescue treatment with albuterol (metered dose inhaler or
nebulizer) as required. These patients were not eligible for a second dose;
however, they had continued FEV1 monitoring in the trial.

Healthy Volunteers: In the healthy volunteer
crossover trial, 30 subjects received 2 doses of either ADASUVE or placebo 8
hours apart, and 2 doses of the alternate treatment at least 4 days later. The
results for maximum decrease in FEV1 are presented in Table 2. No subjects in
this trial developed airway related adverse reactions (cough, wheezing, chest
tightness, or dyspnea).

Asthma Patients: In the asthma trial, 52 patients
with mild-moderate persistent asthma (with FEV1 ≥ 60% of predicted) were
randomized to treatment with 2 doses of ADASUVE 10 mg or placebo. The second
dose was to be administered 10 hours after the first dose. Approximately 67% of
these patients had a baseline FEV1 ≥ 80% of predicted. The remaining
patients had an FEV1 60-80% of predicted. Nine patients (17%) were former
smokers. As shown in Table 2 and Figure 7, there was a marked decrease in FEV1
immediately following the first dose (maximum mean decreases in FEV1 and %
predicted FEV1 were 303 mL and 9.1%, respectively). Furthermore, the effect on
FEV1 was greater following the second dose (maximum mean decreases in FEV1 and
% predicted FEV1 were 537 mL and 14.7 %, respectively). Respiratory-related
adverse reactions (bronchospasm, chest discomfort, cough, dyspnea, throat
tightness, and wheezing) occurred in 54% of ADASUVE-treated patients and 12% of
placebo-treated patients. There were no serious adverse events. Nine of 26
(35%) patients in the ADASUVE group, compared to one of 26 (4%) in the placebo
group, did not receive a second dose of study medication, because they had a
≥ 20% decrease in FEV1 or they developed respiratory symptoms after the
first dose. Rescue medication (albuterol via metered dose inhaler or nebulizer)
was administered to 54% of patients in the ADASUVE group [7 patients (27%)
after the first dose and 7 of the remaining 17 patients (41%) after the second
dose] and 12% in the placebo group (1 patient after the first dose and 2
patients after the second dose).

COPD Patients: In the COPD trial, 53 patients with
mild to severe COPD (with FEV1 ≥ 40% of predicted) were randomized to
treatment with 2 doses of ADASUVE 10 mg or placebo. The second dose was to be
administered 10 hours after the first dose. Approximately 57% of these patients
had moderate COPD [Global Initiative for Chronic Obstructive Lung Disease
(GOLD) Stage II]; 32% had severe disease (GOLD Stage III); and 11% had mild disease
(GOLD Stage I). As illustrated in Table 2 there was a decrease in FEV1 soon
after the first dose (maximum mean decreases in FEV1 and % predicted FEV1 were
96 mL and 3.5%, respectively), and the effect on FEV1 was greater following the
second dose (maximum mean decreases in FEV1 and % predicted FEV1 were 125 mL
and 4.5%, respectively). Respiratory adverse reactions occurred more frequently
in the ADASUVE group (19%) than in the placebo group (11%). There were no
serious adverse events. Seven of 25 (28%) patients in the ADASUVE group and 1of
27 (4%) in the placebo group did not receive a second dose of study medication
because of a ≥ 20% decrease in FEV1 or the development of respiratory
symptoms after the first dose. Rescue medication (albuterol via MDI or
nebulizer) was administered to 23% of patients in the ADASUVE group: 8% of
patients after the first dose and 21% of patients after the second dose, and to
15% of patients in the placebo group.

Table 2: Maximum Decrease in FEV1 from Baseline in the
Healthy Volunteer, Asthma, and COPD Trials

Maximum % FEV↓

Healthy Volunteer

Asthma

COPD

Placebo

ADASUVE 10 mg

Placebo

ADASUVE 10 mg

Placebo

ADASUVE 10 mg

n (%)

n (%)

n (%)

n (%)

n (%)

n (%)

After any Dose

N=26

N=26

N=26

N=26

N=27

N=25

≥ 10

7 (27)

7 (27)

3 (12)

22 (85)

18 (67)

20 (80)

≥ 15

1 (4)

5 (19)

1 (4)

16 (62)

9 (33)

14 (56)

≥ 20

0

1 (4)

1 (4)

11 (42)

3 (11)

10 (40)

After Dose 1

N=26

N=26

N=26

N=26

N=27

N=25

≥ 10

4 (15)

5 (19)

2 (8)

16 (62)

8 (30)

16 (64)

≥ 15

1 (4)

2 (8)

1 (4)

8 (31)

4 (15)

10 (40)

≥ 20

0

0

1 (4)

6 (23)

2 (7)

9 (36)

After Dose 2

N=26

N=25

N=25

N=17

N=26

N=19

≥ 10

5 (19)

6 (24)

3 (12)

12 (71)

15 (58)

12 (63)

≥ 15

0

5 (20)

1 (4)

9 (53)

6 (23)

10 (53)

≥ 20

0

1 (4)

1 (4)

5 (30)

1 (4)

5 (26)

FEV1 categories are cumulative; i.e. a subject with a
maximum decrease of 21% is included in all 3 categories. Patients with a
≥ 20% decrease in FEV1 did not receive a second dose of study drug.

Figure 7: LS Mean Change from Baseline in FEV1 in
Patients with Asthma

Patients with a ≥ 20% decrease in FEV1 did not
receive a second dose of study drug and are not included in the curves beyond
hour 10.

Extrapyramidal Symptoms (EPS): Extrapyramidal
reactions have occurred during the administration of oral loxapine. In most
patients, these reactions involved parkinsonian symptoms such as tremor,
rigidity, and masked facies. Akathisia (motor restlessness) has also occurred.

In the 3 short-term (24-hour), placebo-controlled trials
of ADASUVE in 259 patients with agitation associated with schizophrenia or
bipolar disorder, extrapyramidal reactions occurred. One patient (0.4%) treated
with ADASUVE developed neck dystonia and oculogyration. The incidence of
akathisia was 0% and 0.4% in the placebo and ADASUVE groups, respectively.

Dystonia (Antipsychotic Class Effect): Symptoms of
dystonia, prolonged abnormal contractions of muscle groups, may occur in
susceptible individuals during treatment with ADASUVE. Dystonic symptoms
include spasm of the neck muscles, sometimes progressing to tightness of the
throat, difficulty swallowing or breathing, and/or protrusion of the tongue.

Acute dystonia tends to be dose-related, but can occur at
low doses, and occurs more frequently with first generation antipsychotic drugs
such as ADASUVE. The risk is greater in males and younger age groups.